title: Reggies/flotillins interact with Rab11a and SNX4 at the tubulovesicular recycling compartment and function in transferrin receptor and E-cadherin trafficking.
abstract: The lipid raft proteins reggie-1 and -2 (flotillins) are implicated in membrane protein trafficking but exactly how has been elusive. We find that reggie-1 and -2 associate with the Rab11a, SNX4, and EHD1-decorated tubulovesicular recycling compartment in HeLa cells and that reggie-1 directly interacts with Rab11a and SNX4. Short hairpin RNA-mediated down-regulation of reggie-1 (and -2) in HeLa cells reduces association of Rab11a with tubular structures and impairs recycling of the transferrin-transferrin receptor (TfR) complex to the plasma membrane. Overexpression of constitutively active Rab11a rescues TfR recycling in reggie-deficient HeLa cells. Similarly, in a Ca(2+) switch assay in reggie-depleted A431 cells, internalized E-cadherin is not efficiently recycled to the plasma membrane upon Ca(2+) repletion. E-cadherin recycling is rescued, however, by overexpression of constitutively active Rab11a or SNX4 in reggie-deficient A431 cells. This suggests that the function of reggie-1 in sorting and recycling occurs in association with Rab11a and SNX4. Of interest, impaired recycling in reggie-deficient cells leads to de novo E-cadherin biosynthesis and cell contact reformation, showing that cells have ways to compensate the loss of reggies. Together our results identify reggie-1 as a regulator of the Rab11a/SNX4-controlled sorting and recycling pathway, which is, like reggies, evolutionarily conserved.
authors.affiliation: Department of Biology, University of Konstanz, 78467 Konstanz, Germany. Claudia.Stuermer@uni-konstanz.de
authors.forename: Gonzalo P
authors.initials: GP
authors.lastname: Solis
authors.forename: Nikola
authors.initials: N
authors.lastname: Hülsbusch
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Radon
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Katanaev
authors.forename: Helmut
authors.initials: H
authors.lastname: Plattner
authors.forename: Claudia A O
authors.initials: CA
authors.lastname: Stuermer
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010802:Phylogeny; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism*; D058305:Sorting Nexins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D015820:Cadherins; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D058305:Sorting Nexins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C513981:SNX4 protein, human; C106354:flotillins